基于抗体的肿瘤治疗策略与传统疗法相比,具有更高的靶向选择性和更低的毒副作用。抗体药物偶联物(antibody drug conjugates,ADC)实现了生物大分子抗体和小分子毒素优势的强强联合,被视为未来肿瘤治疗的重要手段。美登素(maytansine)及...基于抗体的肿瘤治疗策略与传统疗法相比,具有更高的靶向选择性和更低的毒副作用。抗体药物偶联物(antibody drug conjugates,ADC)实现了生物大分子抗体和小分子毒素优势的强强联合,被视为未来肿瘤治疗的重要手段。美登素(maytansine)及其衍生物是现阶段ADC应用最广泛的毒素之一,采用该类毒素的ADC药物阿多曲妥珠单抗依酯(ATE)的上市,成功地将ADC的适应证从血癌扩展到其他实体肿瘤。目前,多种该类ADC临床试验进展顺利。本文主要介绍了美登素类ADC各个构件的特征、代谢特征、偶联方法和最新临床试验进展情况。展开更多
抗体药物偶联物(antibody drug conjugates,ADC)是一类具有良好靶向性的抗肿瘤药物,它利用单克隆抗体与高效细胞毒分子的完美结合,最大程度地增加了高效细胞毒分子的治疗窗。近年来,随着Adcetris和Kadcyla两个ADC药物的相继上市,抗体药...抗体药物偶联物(antibody drug conjugates,ADC)是一类具有良好靶向性的抗肿瘤药物,它利用单克隆抗体与高效细胞毒分子的完美结合,最大程度地增加了高效细胞毒分子的治疗窗。近年来,随着Adcetris和Kadcyla两个ADC药物的相继上市,抗体药物偶联物的研究也逐渐成为靶向抗肿瘤治疗领域的一个研究热点。本文对ADC主要组成部件研究进展及上市ADC药物Kadcyla和美登素相关ADC药物的临床试验状况进行综述,并对未来ADC发展趋势进行展望,希望为今后的ADC药物研究工作提供的参考和借鉴。展开更多
Suspension cell cultures of Maytenus hookeri Loos. (Celastraceae) in SH media were established from the calli induced from the leaves and young steins of M. hookeri on MS media with the supplement of 2 mg/L 2,4-D and ...Suspension cell cultures of Maytenus hookeri Loos. (Celastraceae) in SH media were established from the calli induced from the leaves and young steins of M. hookeri on MS media with the supplement of 2 mg/L 2,4-D and 0.1 mg/L KIN (kinetin). Ethyl acetate extract of the cultures showed inhibitory activities against Penicillium avellaneum UC-4376 which was sensitive to maytansinoids. Exhaustive isolation of natural products from a large scale of suspension cell cultures did not yield maytansine instead of affording nine compounds including one novel triterpenoid, named 2, 3-diacetoxyl maytenusone (1), and eight known ones including squalene (2), beta-sitosterol (3), 2', 3', 4-triacetyl-sitoindoside I (4), salaspermic acid (5), maytenonic acid (6), 2alpha-hydroxy-maytenonic acid (7), 6, 11,12-trihydroxy-8, 11, 13-abietrien-7-one (8) and 11, 12-dihydroxy-8, 11, 13-abietatrien-7-one (9) elucidated on the basis of 1D and 2D NMR data. The H-1-NMR and C-13-NMR assignments were made for 1, 5, 6 and 7, while the C-13-NMR assignments for 5 and 6 were revised. The chemical results suggested that the suspension cell cultures of M. hookeri did not produce maytansinoids under the reported experiment conditions.展开更多
文摘基于抗体的肿瘤治疗策略与传统疗法相比,具有更高的靶向选择性和更低的毒副作用。抗体药物偶联物(antibody drug conjugates,ADC)实现了生物大分子抗体和小分子毒素优势的强强联合,被视为未来肿瘤治疗的重要手段。美登素(maytansine)及其衍生物是现阶段ADC应用最广泛的毒素之一,采用该类毒素的ADC药物阿多曲妥珠单抗依酯(ATE)的上市,成功地将ADC的适应证从血癌扩展到其他实体肿瘤。目前,多种该类ADC临床试验进展顺利。本文主要介绍了美登素类ADC各个构件的特征、代谢特征、偶联方法和最新临床试验进展情况。
文摘抗体药物偶联物(antibody drug conjugates,ADC)是一类具有良好靶向性的抗肿瘤药物,它利用单克隆抗体与高效细胞毒分子的完美结合,最大程度地增加了高效细胞毒分子的治疗窗。近年来,随着Adcetris和Kadcyla两个ADC药物的相继上市,抗体药物偶联物的研究也逐渐成为靶向抗肿瘤治疗领域的一个研究热点。本文对ADC主要组成部件研究进展及上市ADC药物Kadcyla和美登素相关ADC药物的临床试验状况进行综述,并对未来ADC发展趋势进行展望,希望为今后的ADC药物研究工作提供的参考和借鉴。
文摘Suspension cell cultures of Maytenus hookeri Loos. (Celastraceae) in SH media were established from the calli induced from the leaves and young steins of M. hookeri on MS media with the supplement of 2 mg/L 2,4-D and 0.1 mg/L KIN (kinetin). Ethyl acetate extract of the cultures showed inhibitory activities against Penicillium avellaneum UC-4376 which was sensitive to maytansinoids. Exhaustive isolation of natural products from a large scale of suspension cell cultures did not yield maytansine instead of affording nine compounds including one novel triterpenoid, named 2, 3-diacetoxyl maytenusone (1), and eight known ones including squalene (2), beta-sitosterol (3), 2', 3', 4-triacetyl-sitoindoside I (4), salaspermic acid (5), maytenonic acid (6), 2alpha-hydroxy-maytenonic acid (7), 6, 11,12-trihydroxy-8, 11, 13-abietrien-7-one (8) and 11, 12-dihydroxy-8, 11, 13-abietatrien-7-one (9) elucidated on the basis of 1D and 2D NMR data. The H-1-NMR and C-13-NMR assignments were made for 1, 5, 6 and 7, while the C-13-NMR assignments for 5 and 6 were revised. The chemical results suggested that the suspension cell cultures of M. hookeri did not produce maytansinoids under the reported experiment conditions.
